crossing96/oncoscreening huggingface dataset:
The common region of lncRNAs UCA1 and UCA1α contributes to the bladder cancer tumorigenesis.	Accumulating evidence suggests that the long noncoding RNAs (lncRNAs) urothelial cancer associated 1 (UCA1) and urothelial cancer associated 1α (UCA1α) play a critical role in the development and progression of bladder cancer. However, the detailed mechanism, in particular the role of the common region of UCA1 and UCA1α, termed UCA1 same sequence (USS, approximately 1265 bp), remains unknown. To address this, the full length of 1265 bp USS was obtained initially, and then produced pcDNA3.1(+)-based overexpression vectors and designed siRNAs for UCA1, UCA1α, and USS, and assessed their effects on the human bladder cancer cell lines UMUC3 (which does not express UCA1 and UCA1α) and 5637 (which has high expression of UCA1 and UCA1α), respectively. Overexpression of UCA1, UCA1α, and USS significantly increased bladder cancer cell proliferation and the number of S-phase cells, but significantly decreased cell apoptosis and the number of G0/G1 phase cells. Consistently, silencing UCA1 and USS significantly decreased bladder cancer cell proliferation and the number of S phase cells, but significantly increased apoptosis and the number of G0/G1 phase cells. These results suggest that USS, the common region of UCA1 and UCA1α, can promote bladder cancer tumorigenesis by increasing cell proliferation and decreasing cell apoptosis in a similar way to UCA1 and UCA1α lncRNAs. This not only transforms our understanding of the role of UCA1, UCA1α, and their common region in tumorigenesis, but may also provide a new target for future clinical applications.	bladder
Improving hexaminolevulinate enabled cancer cell detection in liquid biopsy immunosensors.	Hexaminolevulinate (HAL) induced Protoporphyrin IX (PpIX) fluorescence is commonly used to differentiate cancer cells from normal cells in vivo, as for instance in blue light cystoscopy for bladder cancer diagnosis. A detailed approach is here provided to use this diagnostic principle ex vivo in an immunosensor device, towards enabling non-invasive cancer diagnostic from body fluids, such as urine. Several factors susceptible to affect the applicability of HAL-assisted diagnosis in body fluids were tested. These included the cell viability and its impact on PpIX fluorescence, the storage condition and shelf life of HAL premix reagent, light exposure (360-450 nm wavelengths) and its corresponding effect on both intensity and bleaching of the PpIX fluorescence as a function of the microscopy imaging conditions. There was no significant decrease in the viability of bladder cancer cells after 6 h at 4 °C (student's t-test: p > 0.05). The cellular PpIX fluorescence decreased in a time-dependent manner when cancer cells were kept at 4 °C for extended period of time, though this didn't significantly reduce the fluorescence intensity contrast between cancer and non-cancer cells kept in the same condition for 6 h. HAL premix reagent kept in long term storage at 4 °C induced stronger PpIX fluorescence than reagent kept in the - 20 °C freezer. The PpIX fluorescence was negatively affected by repeated light exposure but increased with illumination intensity and exposure time. Though this applied to both healthy and cancer cell lines, and therefore did not statistically improved the differentiation between cell types. This study revealed important experimental settings that need to be carefully considered to benefit from the analytical potential of HAL induced fluorescence when used in technologies for the diagnosis of cancer from body fluids.	bladder
LINC00649 Facilitates the Cellular Process of Bladder Cancer Cells via Signaling Axis miR-16-5p/JARID2.	Bladder cancer (BC), as one of the most common cancers around the world, begins in the inner side of the bladder and is inclined to spread to the remaining parts of the body. Extensive documents have shown that long noncoding RNAs function as stimuli in various cancer types. With regard to LINC00649, there is limited investigation on its role previously. In our research, we discovered that LINC00649 was considerably highly expressed in BC cells and the lack of LINC00649 would cause inactivity in cellular proliferation, migration, and invasion. miR-16-5p turned out to be competitively incorporated by LINC00649 in the upstream or JARID2 downstream. In BC cells, LINC00649 was found to bind with miR-16-5p to increase the expression of JARID2. Overly expressed JARID2 was found to reverse the LINC00649 shortage-mediated suppressive impacts on the cellular process of BC cells. Concisely, it was the first study on the molecular mechanism of LINC00649 in BC. This work detected that LINC00649 enhanced cell proliferation, migration, and invasion of BC cells by acting as a sponge of miR-16-5p and upregulating JARID2, providing novel insight into understating BC.	bladder
Changes in expression of TLR-4, TGF-β, INF-γ, TNF-α in cultured T24/83 cells of invasive bladder cancer treated with cisplatin and/or polyphenolic adjuvant melanin.	BACKGROUND: Toll-like receptor 4 (TLR4) is known to be involved in carcinogenesis and cancer progression. Changes in TLR4 expression are associated with changes in the expression of key cellular cytokines (transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ)), which affect cancer progression and metastasis. AIM: To study changes in the expression of TLR4, TGF-β, TNF-α, IFN-γ genes, the level of apoptosis and cell cycle distribution in human invasive urothelial carcinoma T24/83 cells under the treatment with polyphenolic adjuvant compound of fungal origin melanin, cytotoxic drug cisplatin, and combination of both. MATERIALS AND METHODS: T24/83 cells were incubated with cisplatin (0.05 mM), melanin (5 µg/ml), or their combination. The expression level of TLR-4, TGF-β, INF-γ, TNF-α was evaluated by the real time polymerase chain reaction. The flow cytometry was used to study cell cycle distribution, proliferative activity and level of apoptosis. Morphological analysis of the Т24/83 cells was performed as well. RESULTS: Melanin, cisplatin, and their combination downregulate TLR4 expression (2.67; 1.28; and 2.73-fold decrease, respectively) and TNF-α expression (6.5; 1.4; and 1.7-fold decrease, respectively). Melanin did not affect TGF-β expression while cisplatin caused 13-fold downregulation of TGF-β. The combined use of cisplatin and melanin decreased TGF-β expression by 6.5 times. The upregulation of IFN-γ by melanin, cisplatin, and their combination was demonstrated (4.3; 6.7; and 2-fold increase, respectively). All treatment modalities increased the level of apoptosis in T24/83 cells. Melanin treatment increased significantly the proportion of fibroblast-like cells in T24/83 culture with decreased cell adhesion to the substrate. CONCLUSIONS: Melanin, cisplatin, and combination of both agents affect significantly TLR4, TNF-α, TGF-β, INF-γ expression, cell cycle distribution and morphology in T24/83 cells suggesting their transition to less aggressive phenotype.	bladder
BBN-driven urinary bladder cancer mouse model.	Around 3% of new cancer diagnoses and 2% of all cancer deaths every year are caused by urinary bladder cancer (BC). This indicates a great need for intensive studying of BC by using different approaches including indispensable mice models. The most common preclinical mouse model of bladder carcinogenesis relies on the use of a nitrosamine compound, N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) which causes high-grade, invasive tumors in the urinary bladder. BBN-induced bladder cancer in mice recapitulates the histology and manifests genetic alterations similar to human muscle-invasive bladder cancer. Here we present a detailed protocol for the induction of BC in mice which is based on the administration of 0.05%-0.1% BBN in drinking water. Six-to-eight-week-old mice are treated orally with BBN for 12weeks and tumors are expected 8weeks after the termination of BBN regimen. Histopathologic examination of the lesions should be routinely assessed after hematoxylin and eosin staining by an experienced pathologist and it can vary from urothelial dysplasia to invasive bladder cancer with glandular and squamous divergent differentiation, the incidence of which might depend on the mouse strain, gender, BBN concentration and the timeline of the protocol. Utilizing half of the urinary bladder tissue for the isolation and analysis of RNA, DNA and proteins provides a comprehensive insight into the biology of BC and reduces the number of mice per study. Finally, the successful use of the BC model can facilitate fundamental biomedical discoveries leading to novel diagnostic and therapeutic approaches with clinical benefits.	bladder
No Outcome Differences after Cystectomy between Patients with De Novo Muscle-Invasive Bladder Cancer Compared to Progressors: A Retrospective Population-Based Study.	PURPOSE: Whether patients who progress to muscle-invasive bladder cancer have worse outcomes compared to those that present de novo is important for clinical decision making. The objective of this study was to determine if there is a difference in survival after radical cystectomy for de novo cases compared to progressors. MATERIALS AND METHODS: This retrospective, population-based study reports on all patients who underwent radical cystectomy in Ontario utilizing records linked to the Ontario Cancer Registry. The primary objective was to determine if survival was associated with presentation. Secondary objectives included describing processes-of-care between the cohorts and investigate differential responses to chemotherapy. Cox proportional-hazards regression models were used to adjust for known confounders. RESULTS: Between 2009 and 2013, 1,573 patients underwent radical cystectomy with 893 in the de novo cohort while 680 were identified as progressors. After adjusting by stage prior to cystectomy, several processes of care indicators and early outcomes were comparable between the cohorts. In adjusted analysis there were no differences in outcomes; compared to the reference de novo presentation, the hazards ratios (95% confidence interval) for progressors were 0.98 (0.85-1.14) for cancer-specific survival and 1.0 (0.88-1.10) for overall survival. There was no effect modification of chemotherapy based on presentation for cancer-specific survival. Lack of information about those progressors that never received cystectomy is a major limitation. CONCLUSIONS: When controlled for stage, no clinically significant differences in survival outcomes were identified between bladder cancer patients undergoing cystectomy presenting with de novo muscle-invasive bladder cancer compared to progressors in routine clinical practice.	bladder
Impact of paclitaxel, cisplatin, and gemcitabine as first-line chemotherapy in cisplatin-fit and -unfit patients with advanced/metastatic urothelial carcinoma.	PURPOSE: This study aimed to clarify the efficacy and toxicity of first-line combination treatment with paclitaxel, cisplatin, and gemcitabine (PCG) for advanced/metastatic urothelial carcinoma (UC) in cisplatin-unfit patients compared with cisplatin-fit patients. METHODS: We conducted a retrospective study of patients who received first-line PCG. Using international consensus criteria, patients were classified into cisplatin-fit and -unfit groups. Cisplatin-unfit patients received PCG with adjustment of the cisplatin dose after assessing 24-hour urinary creatinine clearance, without modifying the administration interval. RESULTS: From 2008 to 2017, 50 patients received first-line PCG, of whom 30 and 20 were classified into the cisplatin-fit and -unfit groups. After a median follow-up of 15.0 months, the median overall survival (OS) and progression-free survival (PFS) were 15.0 and 9.8 months in all patients, 15.0 and 10.0 months in the cisplatin-fit group, and 13.2 and 9.3 months in the cisplatin-unfit group, respectively. There was no significant difference in OS (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 0.69-2.54) or PFS (HR: 1.38, 95% CI: 0.74-2.55) between the groups. The overall response rate and complete response rate were 58% (95% CI: 43.2-71.8) and 32% (95% CI: 19.5-46.7) in all patients, and 55% (95% CI: 31.5-76.9) and 35% (95% CI: 15.4-59.2) in the cisplatin-unfit group, respectively. The common grade 3 of 4 adverse events experienced were neutropenia (78%), followed by thrombocytopenia (56%), anemia (46%), and febrile neutropenia (16%). The 24-hour urinary creatinine clearance did not differ significantly between the groups after one, two, or three courses of PCG. CONCLUSIONS: We found no significant difference regarding OS and PFS between the cisplatin-fit patients with a full dose of cisplatin and -unfit patients with cisplatin-dose-adjusted chemotherapy. In select cisplatin-unfit patients, PCG with dose adjustment of cisplatin may be useful for treating advanced/metastatic UC without any significant adverse events or impaired renal function compared with cisplatin-fit patients with a full dose of cisplatin.	bladder
Trans-sulcal parafascicular approach to subcortical lesions.	Historically, neoplasms which are located in the subcortical region of the brain are considered technically difficult to access. As such, tumours in these locations are usually avoided, due to the risks associated with traversing eloquent cortex, the disrupting of white matter tracts, or the need to use narrow corridors to approach the lesion. Tubular retractors are able to gently displace brain parenchyma and white matter in an atraumatic fashion to access these deep regions. We demonstrate a minimally invasive trans-sulcal parafascicular approach using the Brainpath system (NICO Corp, Indianapolis, Indiana) to a caudate head metastasis as a representative case.	bladder
Immunohistochemistry as a paramount tool in research of normal urothelium, bladder cancer and bladder pain syndrome.	The urothelium, an epithelium of the urinary bladder, primarily functions as blood-urine permeability barrier. The urothelium has a very slow turn-over under normal conditions but is capable of extremely fast response to injury. During regeneration urothelium either restores normal function or undergoes altered differentiation pathways, the latter being the cause of several bladder diseases. In this review, we describe the structure of the apical plasma membrane that enables barrier function, the role of urothelium specific proteins uroplakins and the machinery for polarized membrane transports in terminally differentiated superficial umbrella cells. We address key markers, such as keratins, cancer stem cell markers, retinoic acid signalling pathway proteins and transient receptor potential channels and purinergic receptors that drive normal and altered differentiation in bladder cancer and bladder pain syndrome. Finally, we discuss uncertainties regarding research, diagnosis and treatment of bladder pain syndrome. Throughout the review, we emphasise the contribution of immunohistochemistry in advancing our understanding of processes in normal and diseased bladder as well as the most promising possibilities for improved bladder cancer and bladder pain syndrome management.	bladder
Effect of NCOR1 Mutations on Immune Microenvironment and Efficacy of Immune Checkpoint Inhibitors in Patient with Bladder Cancer.	Immune checkpoint blockade (ICB) therapy has significantly progressed the treatment of bladder cancer (BLCA). Multiple studies have suggested that specific genetic mutations may serve as immune biomarkers for ICB therapy. Additionally, the nuclear receptor corepressor 1 (NCOR1) gene is a new player in the field of immune tolerance and the development of immune cells. In the ICI-treated-cohort, NCOR1 mutations may be used as a biomarker to predict the prognosis of BLCA patients receiving ICIs. The overall survival (OS) of the NCOR1-mutant (NCOR1-MT) group was significantly longer than that of NCOR1-wild-type (NCOR1-WT) group (P = 0·031; HR [95%CI]: 0·25 [0·12-0·52]). In the TCGA-BLCA-cohort, compared with NCOR1-WT, NCOR1-MT was associated with known predictors of ICB therapy efficacy, such as higher tumor mutational burden (TMB), neoantigen load and the number of mutations in the DNA damage-repair pathway. In addition, NCOR1-MT tumors had highly infiltrating TILs, activated antitumor immunity, and a high expression of immune-related genes, suggesting that NCOR1 mutations may serve as a potential biomarker to guide ICB therapy in BLCA.	bladder
Lipid-rich variant of urothelial carcinoma: a lethal enigma.	Invasive urothelial carcinoma shows marked propensity for divergent differentiation. Several of these 'variant' morphologies have been described in literature and recognised in the 2004 WHO classification. In this report, we detail a case of bladder tumour, diagnosed to be a lipid-rich variant on histopathology after transurethral resection of bladder tumour. Our case encompasses the complete clinical spectrum of this rare and aggressive subtype of urothelial carcinoma starting from initial presentation to postoperative follow-up and recurrence. A keen eye for recognising these variants can ensure a timely diagnosis of these variant and administration of a therapy distinctive from that used in conventional invasive urothelial carcinoma.	bladder
Bacillus Calmette-Guerin vaccine and bladder cancer incidence: Scoping literature review and preliminary analysis.	BACKGROUND: The Bacillus Calmette-Guerin (BCG) vaccine has long been used for the prevention of tuberculosis (TB) around the world. BCG is also used as an immunotherapy agent for the treatment of non-muscle invasive urinary bladder cancer. This scoping literature review and preliminary data analysis aims to summarize the literature correlating infantile BCG vaccination with the incidence of future bladder cancer. METHODS: Studies were identified by a formal literature search of MEDLINE and Cochrane Central Registrar of Controlled Trials following PRISMA guidelines. Preliminary data analysis was conducted on publicly accessible data summarizing the impact of gender, BCG vaccination, and socio-economic effects on crude and age-standardized rates of bladder cancer. RESULTS: As part of our analysis, preliminary regression models demonstrated BCG vaccination status, gender, and socio-economic status to have statistically significant effects on crude and age-standardized rates of bladder cancer incidence. BCG vaccination was associated with a 35-37% lower age-standardized rate of bladder cancer incidence. CONCLUSIONS: There is very little literature examining the relationship between prior BCG vaccination and rates of bladder cancer incidence. Our limited data analysis indicates that a relationship does exist between infantile BCG vaccination and later bladder cancer development, although extensive future investigation is needed in this area.	bladder
Ultra-rapid regrowth of urothelial cardiac metastasis after debulking surgery.	Cardiac metastases of urothelial carcinoma are a rare manifestation, and most of them are asymptomatic or autoptic findings. We report a case of a 64-year-old Caucasian man fully asymptomatic, who has been accidentally diagnosed with a right atrial mass during his routine follow up for previous urothelial cancer. Endomyocardial biopsy, and histological examination of the mass were crucial to reach a definitive diagnosis of urothelial metastasis. He underwent a debulking surgery of the mass to avoid cardiac life-threatening complications. Despite effective removal of the atrial metastasis, after 45 days the patient experienced an ultra-rapid regrowth of the mass in the same position. This case demonstrates how rapidly a urothelial cardiac metastasis can grow back, and that surgery does not avoid by itself early recurrence.	bladder
Efficacy of immune-checkpoint inhibitors in PD-L1 selected or unselected patients vs. control group in patients with advanced or metastatic urothelial carcinoma.	Most patients with advanced or metastatic urothelial carcinoma do not benefit significantly from Immune checkpoint inhibitors (ICIs) use. A systematic review and meta-analysis of randomized controlled trials to assess the efficacy and activity of ICIs, in terms of Overall Survival (OS), Progression-free survival (PFS), and Objective Response Rate (ORR). We systematically searched for articles from PubMed, Cochrane Library, Embase, and Web of science from their inception to December 1, 2020 with no language restrictions. The search was performed to identify all clinical trials (phase I, phase II, phase III) of ICIs for treating urothelial carcinoma. The endpoints of the meta-analysis were OS, PFS, and ORR, compared unselected patients and in the subgroup of patients characterized by high expression of PD-L1 (PD-L1 selected patients). Sixteen studies comprising 5559 patients were identified, of which data for OS comparison were available from 4 RCTs (2342 patients), two studies for PFS (649 patients), and four RCTs were eligible for ORR analysis (2921 patients). Both pembrolizumab and atezolizumab have showed to improve OS compared to chemotherapy in unselected patients (HR 0.86, 95% CI 0.80-0.93, P = .0001, I(2) = 60%), while the difference was not significant in PD-L1 selected patients (HR 0.91, 95% CI 0.77-1.07, P = .23, I(2) = 0%). PFS difference was not observed in neither unselected population nor PD-L1 selected patients, the pooled HR of PFS for immunotherapy compared to control treatment was 1.05 (95% CI 0.74-1.49, P = .79, I(2) = 85%) and 0.84 (95% CI 0.68-1.03, P = .09, I(2) = 0%, respectively. Similar result was observed in ORR, the pooled HR of ORR for immunotherapy compared to control treatment was 1.45 (95% CI 0.53-3.98, P = .47, I(2) = 95%) and 2.19 (95% CI 0.79-6.08, P = .13, I(2) = 83%), respectively. Immunotherapy could significantly improve survival advantage in unselected patients but not in PD-L1 selected population, indicating that PD-L1 expression may not be a reliable marker in previously platinum-treated patients.	bladder
Tertiary lymphoid structures marker CXCL13 is associated with better survival for patients with advanced-stage bladder cancer treated with immunotherapy.	INTRODUCTION: Immune checkpoint inhibitors (ICIs) have proved to be an effective treatment for up to 40% of muscle-invasive bladder cancer (MIBC), but there is still a need for better performing biomarkers allowing to improve prediction of response to ICI. Response to immunotherapy in soft-tissue sarcoma, melanoma and renal cell carcinoma have been recently linked to the presence of tertiary lymphoid structures (TLS) in the tumour. TLS are organised aggregates of T, B and dendritic cells, participating in adaptive antitumor immune response. The chemokine CXCL13 is involved in the formation of TLS, and is reported as a reliable transcriptomic marker of TLS. OBJECTIVES: In this study, we sought to assess whether CXCL13 transcript expression can be a prognostic biomarker for ICI-treated MIBC patients and also investigated whether it can serve a biomarker of TLS in MIBC. METHODS: We analysed transcriptomic data from three publicly available MIBC cohorts and evaluated pathological slides from the TCGA-BLCA cohort for TLS presence and stage of maturation. RESULTS: We showed that CXCL13 was independently associated with both prolonged survival (HR = 0.8, 95% CI [0.68-0.94]) and objective response (p < 0.0001) in patients treated with ICI, at the difference of others immunological signatures. However, it was not a predictor for non-ICI-treated MIBC, suggesting a predictive effect of ICI efficacy. Finally, we validated that CXCL13 expression was correlated with tumour TLS in TCGA data set (p < 0.001), and can serve as a marker of TLS in bladder cancer. CONCLUSION: These results support that CXCL13 expression, as a surrogate for tumour TLS, is a relevant candidate predictive biomarker of response to ICI for patients with advanced-stage bladder cancer.	bladder